{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T04:19:54Z","timestamp":1790741994379,"version":"4.1.0"},"reference-count":106,"publisher":"Elsevier BV","issue":"22","license":[{"start":{"date-parts":[[2024,10,1]],"date-time":"2024-10-01T00:00:00Z","timestamp":1727740800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2024,10,1]],"date-time":"2024-10-01T00:00:00Z","timestamp":1727740800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2024,8,20]],"date-time":"2024-08-20T00:00:00Z","timestamp":1724112000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100010663","name":"European Research Council","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100010663","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["cell.com","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Cell"],"published-print":{"date-parts":[[2024,10]]},"DOI":"10.1016\/j.cell.2024.08.034","type":"journal-article","created":{"date-parts":[[2024,9,17]],"date-time":"2024-09-17T18:33:40Z","timestamp":1726598020000},"page":"6220-6234.e13","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":23,"title":["In\u00a0vivo DNA replication dynamics unveil aging-dependent replication stress"],"prefix":"10.1016","volume":"187","author":[{"given":"Giacomo G.","family":"Rossetti","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"No\u00eblle","family":"Dommann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angeliki","family":"Karamichali","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vasilis S.","family":"Dionellis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ainhoa","family":"Asensio Aldave","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tural","family":"Yarahmadov","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eddie","family":"Rodriguez-Carballo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adrian","family":"Keogh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Candinas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deborah","family":"Stroka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8384-5030","authenticated-orcid":false,"given":"Thanos D.","family":"Halazonetis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.cell.2024.08.034_bib1","doi-asserted-by":"crossref","first-page":"646","DOI":"10.1016\/j.cell.2011.02.013","article-title":"Hallmarks of cancer: the next generation","volume":"144","author":"Hanahan","year":"2011","journal-title":"Cell"},{"key":"10.1016\/j.cell.2024.08.034_bib2","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1038\/nrm2858","article-title":"Genomic instability--an evolving hallmark of cancer","volume":"11","author":"Negrini","year":"2010","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"10.1016\/j.cell.2024.08.034_bib3","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1126\/science.1253462","article-title":"Spatial and temporal diversity in genomic instability processes defines lung cancer evolution","volume":"346","author":"de Bruin","year":"2014","journal-title":"Science"},{"key":"10.1016\/j.cell.2024.08.034_bib4","doi-asserted-by":"crossref","first-page":"2239","DOI":"10.1016\/j.cell.2021.03.009","article-title":"Characterizing genetic intra-tumor heterogeneity across 2,658 human cancer genomes","volume":"184","author":"Dentro","year":"2021","journal-title":"Cell"},{"key":"10.1016\/j.cell.2024.08.034_bib5","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1016\/j.cell.2022.11.001","article-title":"Hallmarks of aging: an expanding universe","volume":"186","author":"L\u00f3pez-Ot\u00edn","year":"2023","journal-title":"Cell"},{"key":"10.1016\/j.cell.2024.08.034_bib6","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1016\/j.cell.2005.01.027","article-title":"Understanding the odd science of aging","volume":"120","author":"Kirkwood","year":"2005","journal-title":"Cell"},{"key":"10.1016\/j.cell.2024.08.034_bib7","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1016\/j.cell.2005.01.028","article-title":"DNA repair, genome stability, and aging","volume":"120","author":"Lombard","year":"2005","journal-title":"Cell"},{"key":"10.1016\/j.cell.2024.08.034_bib8","doi-asserted-by":"crossref","first-page":"695","DOI":"10.1038\/s41586-021-03307-7","article-title":"The central role of DNA damage in the ageing process","volume":"592","author":"Schumacher","year":"2021","journal-title":"Nature"},{"key":"10.1016\/j.cell.2024.08.034_bib9","doi-asserted-by":"crossref","first-page":"1897","DOI":"10.1126\/science.286.5446.1897","article-title":"Quality control by DNA repair","volume":"286","author":"Lindahl","year":"1999","journal-title":"Science"},{"key":"10.1016\/j.cell.2024.08.034_bib10","doi-asserted-by":"crossref","first-page":"366","DOI":"10.1038\/35077232","article-title":"Genome maintenance mechanisms for preventing cancer","volume":"411","author":"Hoeijmakers","year":"2001","journal-title":"Nature"},{"key":"10.1016\/j.cell.2024.08.034_bib11","doi-asserted-by":"crossref","first-page":"1071","DOI":"10.1038\/nature08467","article-title":"The DNA-damage response in human biology and disease","volume":"461","author":"Jackson","year":"2009","journal-title":"Nature"},{"key":"10.1016\/j.cell.2024.08.034_bib12","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1038\/nrm2852","article-title":"Maintaining genome stability at the replication fork","volume":"11","author":"Branzei","year":"2010","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"10.1016\/j.cell.2024.08.034_bib13","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1038\/ncb2897","article-title":"Causes and consequences of replication stress","volume":"16","author":"Zeman","year":"2014","journal-title":"Nat. Cell Biol."},{"key":"10.1016\/j.cell.2024.08.034_bib14","doi-asserted-by":"crossref","first-page":"1049","DOI":"10.1016\/j.bbapap.2009.06.012","article-title":"DNA polymerase proofreading: multiple roles maintain genome stability","volume":"1804","author":"Reha-Krantz","year":"2010","journal-title":"Biochim. Biophys. Acta"},{"key":"10.1016\/j.cell.2024.08.034_bib15","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1083\/jcb.201407004","article-title":"Peaks cloaked in the mist: the landscape of mammalian replication origins","volume":"208","author":"Hyrien","year":"2015","journal-title":"J.\u00a0Cell Biol."},{"key":"10.1016\/j.cell.2024.08.034_bib16","doi-asserted-by":"crossref","first-page":"1683","DOI":"10.1101\/gad.285114.116","article-title":"DNA replication origins-where do we begin?","volume":"30","author":"Prioleau","year":"2016","journal-title":"Genes Dev."},{"key":"10.1016\/j.cell.2024.08.034_bib17","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1016\/j.ceb.2019.03.003","article-title":"Metazoan DNA replication origins","volume":"58","author":"Ganier","year":"2019","journal-title":"Curr. Opin. Cell Biol."},{"key":"10.1016\/j.cell.2024.08.034_bib18","doi-asserted-by":"crossref","first-page":"352","DOI":"10.1016\/j.molcel.2022.12.024","article-title":"Origins of DNA replication in eukaryotes","volume":"83","author":"Hu","year":"2023","journal-title":"Mol. Cell"},{"key":"10.1016\/j.cell.2024.08.034_bib19","doi-asserted-by":"crossref","DOI":"10.1038\/ncomms10208","article-title":"Replication landscape of the human genome","volume":"7","author":"Petryk","year":"2016","journal-title":"Nat. Commun."},{"key":"10.1016\/j.cell.2024.08.034_bib20","first-page":"10230","article-title":"Genome-wide identification and characterisation of human DNA replication origins by initiation site sequencing (ini-seq)","volume":"44","author":"Langley","year":"2016","journal-title":"Nucleic Acids Res."},{"key":"10.1016\/j.cell.2024.08.034_bib21","doi-asserted-by":"crossref","first-page":"7436","DOI":"10.1093\/nar\/gkac555","article-title":"Determination of human DNA replication origin position and efficiency reveals principles of initiation zone organisation","volume":"50","author":"Guilbaud","year":"2022","journal-title":"Nucleic Acids Res."},{"key":"10.1016\/j.cell.2024.08.034_bib22","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1007\/s10577-019-09624-y","article-title":"Genomic methods for measuring DNA replication dynamics","volume":"28","author":"Hulke","year":"2020","journal-title":"Chromosome Res."},{"key":"10.1016\/j.cell.2024.08.034_bib23","article-title":"Integrative analysis of DNA replication origins and ORC\/MCM binding sites in human cells reveals a lack of overlap","author":"Tian","year":"2023","journal-title":"bioRxiv"},{"key":"10.1016\/j.cell.2024.08.034_bib24","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1038\/s41594-018-0171-0","article-title":"Transcription shapes DNA replication initiation and termination in human cells","volume":"26","author":"Chen","year":"2019","journal-title":"Nat. Struct. Mol. Biol."},{"key":"10.1016\/j.cell.2024.08.034_bib25","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1186\/s13059-020-01983-8","article-title":"High-resolution Repli-Seq defines the temporal choreography of initiation, elongation and termination of replication in mammalian cells","volume":"21","author":"Zhao","year":"2020","journal-title":"Genome Biol."},{"key":"10.1016\/j.cell.2024.08.034_bib26","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pcbi.1011138","article-title":"Neural network and kinetic modelling of human genome replication reveal replication origin locations and strengths","volume":"19","author":"Arbona","year":"2023","journal-title":"PLoS Comput. Biol."},{"key":"10.1016\/j.cell.2024.08.034_bib27","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1038\/nature25507","article-title":"Intragenic origins due to short G1 phases underlie oncogene-induced DNA replication stress","volume":"555","author":"Macheret","year":"2018","journal-title":"Nature"},{"key":"10.1016\/j.cell.2024.08.034_bib28","doi-asserted-by":"crossref","first-page":"1438","DOI":"10.1101\/gr.121830.111","article-title":"Genome-scale analysis of metazoan replication origins reveals their organization in specific but flexible sites defined by conserved features","volume":"21","author":"Cayrou","year":"2011","journal-title":"Genome Res."},{"key":"10.1016\/j.cell.2024.08.034_bib29","doi-asserted-by":"crossref","DOI":"10.1038\/s41467-020-18527-0","article-title":"A predictable conserved DNA base composition signature defines human core DNA replication origins","volume":"11","author":"Akerman","year":"2020","journal-title":"Nat. Commun."},{"key":"10.1016\/j.cell.2024.08.034_bib30","doi-asserted-by":"crossref","DOI":"10.1126\/sciadv.add3686","article-title":"DNA replication initiation shapes the mutational landscape and expression of the human genome","volume":"8","author":"Murat","year":"2022","journal-title":"Sci. Adv."},{"key":"10.1016\/j.cell.2024.08.034_bib31","doi-asserted-by":"crossref","first-page":"836","DOI":"10.1038\/nrm1489","article-title":"Liver regeneration: from myth to mechanism","volume":"5","author":"Taub","year":"2004","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"10.1016\/j.cell.2024.08.034_bib32","doi-asserted-by":"crossref","first-page":"S45","DOI":"10.1002\/hep.20969","article-title":"Liver regeneration","volume":"43","author":"Fausto","year":"2006","journal-title":"Hepatology"},{"key":"10.1016\/j.cell.2024.08.034_bib33","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1038\/s41575-020-0342-4","article-title":"Liver regeneration: biological and pathological mechanisms and implications","volume":"18","author":"Michalopoulos","year":"2021","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"10.1016\/j.cell.2024.08.034_bib34","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1038\/s41596-018-0081-y","article-title":"Monitoring early S-phase origin firing and replication fork movement by sequencing nascent DNA from synchronized cells","volume":"14","author":"Macheret","year":"2019","journal-title":"Nat. Protoc."},{"key":"10.1016\/j.cell.2024.08.034_bib35","doi-asserted-by":"crossref","first-page":"686","DOI":"10.1126\/science.6719109","article-title":"Replication timing of genes and middle repetitive sequences","volume":"224","author":"Goldman","year":"1984","journal-title":"Science"},{"key":"10.1016\/j.cell.2024.08.034_bib36","doi-asserted-by":"crossref","first-page":"17771","DOI":"10.1073\/pnas.0408170101","article-title":"DNA replication-timing analysis of human chromosome 22 at high resolution and different developmental states","volume":"101","author":"White","year":"2004","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1016\/j.cell.2024.08.034_bib37","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1016\/j.gde.2009.02.002","article-title":"Replication timing and transcriptional control: beyond cause and effect\u2014part II","volume":"19","author":"Hiratani","year":"2009","journal-title":"Curr. Opin. Genet. Dev."},{"key":"10.1016\/j.cell.2024.08.034_bib38","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1016\/j.ceb.2010.03.007","article-title":"Interplay between DNA replication and gene expression: a harmonious coexistence","volume":"22","author":"Maric","year":"2010","journal-title":"Curr. Opin. Cell Biol."},{"key":"10.1016\/j.cell.2024.08.034_bib39","doi-asserted-by":"crossref","first-page":"721","DOI":"10.1038\/s41580-019-0162-y","article-title":"Control of DNA replication timing in the 3D genome","volume":"20","author":"Marchal","year":"2019","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"10.1016\/j.cell.2024.08.034_bib40","doi-asserted-by":"crossref","first-page":"3059","DOI":"10.1091\/mbc.e06-08-0689","article-title":"Replication fork velocities at adjacent replication origins are coordinately modified during DNA replication in human cells","volume":"18","author":"Conti","year":"2007","journal-title":"Mol. Biol. Cell"},{"key":"10.1016\/j.cell.2024.08.034_bib41","doi-asserted-by":"crossref","first-page":"3331","DOI":"10.1101\/gad.457807","article-title":"Dormant origins licensed by excess Mcm2-7 are required for human cells to survive replicative stress","volume":"21","author":"Ge","year":"2007","journal-title":"Genes Dev."},{"key":"10.1016\/j.cell.2024.08.034_bib42","doi-asserted-by":"crossref","first-page":"8956","DOI":"10.1073\/pnas.0803978105","article-title":"Excess MCM proteins protect human cells from replicative stress by licensing backup origins of replication","volume":"105","author":"Ibarra","year":"2008","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1016\/j.cell.2024.08.034_bib43","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1101\/gad.2029711","article-title":"The effect of the intra-S-phase checkpoint on origins of replication in human cells","volume":"25","author":"Karnani","year":"2011","journal-title":"Genes Dev."},{"key":"10.1016\/j.cell.2024.08.034_bib44","doi-asserted-by":"crossref","first-page":"6683","DOI":"10.1093\/nar\/gky476","article-title":"Genome-wide analysis of the spatiotemporal regulation of firing and dormant replication origins in human cells","volume":"46","author":"Sugimoto","year":"2018","journal-title":"Nucleic Acids Res."},{"key":"10.1016\/j.cell.2024.08.034_bib45","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1101\/gad.14.4.397","article-title":"ATR disruption leads to chromosomal fragmentation and early embryonic lethality","volume":"14","author":"Brown","year":"2000","journal-title":"Genes Dev."},{"key":"10.1016\/j.cell.2024.08.034_bib46","doi-asserted-by":"crossref","first-page":"622","DOI":"10.1038\/nrm.2017.67","article-title":"The essential kinase ATR: ensuring faithful duplication of a challenging genome","volume":"18","author":"Saldivar","year":"2017","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"10.1016\/j.cell.2024.08.034_bib47","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1158\/1535-7163.MCT-19-0019","article-title":"The novel ATR inhibitor BAY 1895344 is efficacious as monotherapy and combined with DNA damage-inducing or repair-compromising therapies in preclinical cancer models","volume":"19","author":"Wengner","year":"2020","journal-title":"Mol. Cancer Ther."},{"key":"10.1016\/j.cell.2024.08.034_bib48","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1158\/2159-8290.CD-20-0868","article-title":"First-in-human trial of the oral ataxia telangiectasia and RAD3-related (ATR) inhibitor BAY 1895344 in patients with advanced solid tumors","volume":"11","author":"Yap","year":"2021","journal-title":"Cancer Discov."},{"key":"10.1016\/j.cell.2024.08.034_bib49","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1002\/jcp.1041180302","article-title":"Delayed and reduced cell replication and diminishing levels of DNA polymerase-alpha in regenerating liver of aging mice","volume":"118","author":"Fry","year":"1984","journal-title":"J.\u00a0Cell. Physiol."},{"key":"10.1016\/j.cell.2024.08.034_bib50","doi-asserted-by":"crossref","first-page":"1217","DOI":"10.1111\/jgh.12930","article-title":"Dysfunction of liver regeneration in aged liver after partial hepatectomy","volume":"30","author":"Enkhbold","year":"2015","journal-title":"J.\u00a0Gastroenterol. Hepatol."},{"key":"10.1016\/j.cell.2024.08.034_bib51","doi-asserted-by":"crossref","first-page":"9796","DOI":"10.1007\/s11357-015-9796-7","article-title":"Global gene expression profile of normal and regenerating liver in young and old mice","volume":"37","author":"Pibiri","year":"2015","journal-title":"Age (Dordr)"},{"key":"10.1016\/j.cell.2024.08.034_bib52","doi-asserted-by":"crossref","first-page":"615","DOI":"10.1038\/27001","article-title":"A Mec1- and Rad53-dependent checkpoint controls late-firing origins of DNA replication","volume":"395","author":"Santocanale","year":"1998","journal-title":"Nature"},{"key":"10.1016\/j.cell.2024.08.034_bib53","doi-asserted-by":"crossref","first-page":"8552","DOI":"10.1128\/MCB.22.24.8552-8561.2002","article-title":"An ATR- and Chk1-dependent S checkpoint inhibits replicon initiation following UVC-induced DNA damage","volume":"22","author":"Heffernan","year":"2002","journal-title":"Mol. Cell. Biol."},{"key":"10.1016\/j.cell.2024.08.034_bib54","doi-asserted-by":"crossref","first-page":"474","DOI":"10.1038\/nature09373","article-title":"Checkpoint-dependent inhibition of DNA replication initiation by Sld3 and Dbf4 phosphorylation","volume":"467","author":"Zegerman","year":"2010","journal-title":"Nature"},{"key":"10.1016\/j.cell.2024.08.034_bib55","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1016\/S1097-2765(02)00799-2","article-title":"An ATR- and Cdc7-dependent DNA damage checkpoint that inhibits initiation of DNA replication","volume":"11","author":"Costanzo","year":"2003","journal-title":"Mol. Cell"},{"key":"10.1016\/j.cell.2024.08.034_bib56","doi-asserted-by":"crossref","first-page":"2531","DOI":"10.1074\/jbc.M111.291104","article-title":"Dbf4 is direct downstream target of ataxia telangiectasia mutated (ATM) and ataxia telangiectasia and Rad3-related (ATR) protein to regulate intra-S-phase checkpoint","volume":"287","author":"Lee","year":"2012","journal-title":"J.\u00a0Biol. Chem."},{"key":"10.1016\/j.cell.2024.08.034_bib57","doi-asserted-by":"crossref","first-page":"13374","DOI":"10.1073\/pnas.1903418116","article-title":"An ATR and CHK1 kinase signaling mechanism that limits origin firing during unperturbed DNA replication","volume":"116","author":"Moiseeva","year":"2019","journal-title":"Proc. Natl.\u00a0Acad. Sci. USA"},{"key":"10.1016\/j.cell.2024.08.034_bib58","doi-asserted-by":"crossref","DOI":"10.1016\/j.celrep.2020.108096","article-title":"ATR restrains DNA synthesis and mitotic catastrophe in response to CDC7 inhibition","volume":"32","author":"Rainey","year":"2020","journal-title":"Cell Rep."},{"key":"10.1016\/j.cell.2024.08.034_bib59","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1016\/j.gde.2021.07.003","article-title":"An extending ATR-CHK1 circuitry: the replication stress response and beyond","volume":"71","author":"Simoneau","year":"2021","journal-title":"Curr. Opin. Genet. Dev."},{"key":"10.1016\/j.cell.2024.08.034_bib60","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pgen.1001011","article-title":"Comparative analysis of DNA replication timing reveals conserved large-scale chromosomal architecture","volume":"6","author":"Yaffe","year":"2010","journal-title":"PLoS Genet."},{"key":"10.1016\/j.cell.2024.08.034_bib61","doi-asserted-by":"crossref","first-page":"6279","DOI":"10.1158\/0008-5472.CAN-12-3869","article-title":"A single-nucleotide substitution mutator phenotype revealed by exome sequencing of human colon adenomas","volume":"72","author":"Nikolaev","year":"2012","journal-title":"Cancer Res."},{"key":"10.1016\/j.cell.2024.08.034_bib62","doi-asserted-by":"crossref","first-page":"1267","DOI":"10.1038\/sj.emboj.7600602","article-title":"Impairment of replication fork progression mediates RNA polII transcription-associated recombination","volume":"24","author":"Prado","year":"2005","journal-title":"EMBO J."},{"key":"10.1016\/j.cell.2024.08.034_bib63","doi-asserted-by":"crossref","first-page":"1315","DOI":"10.1038\/ncb1984","article-title":"Topoisomerase I suppresses genomic instability by preventing interference between replication and transcription","volume":"11","author":"Tuduri","year":"2009","journal-title":"Nat. Cell Biol."},{"key":"10.1016\/j.cell.2024.08.034_bib64","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1038\/nrg3152","article-title":"Transcription as a source of genome instability","volume":"13","author":"Kim","year":"2012","journal-title":"Nat. Rev. Genet."},{"key":"10.1016\/j.cell.2024.08.034_bib65","doi-asserted-by":"crossref","first-page":"774","DOI":"10.1016\/j.cell.2017.07.043","article-title":"Transcription-replication conflict orientation modulates R-loop levels and activates distinct DNA damage responses","volume":"170","author":"Hamperl","year":"2017","journal-title":"Cell"},{"key":"10.1016\/j.cell.2024.08.034_bib66","doi-asserted-by":"crossref","DOI":"10.3390\/biom11081249","article-title":"Transcription-replication collisions-a series of unfortunate events","volume":"11","author":"St Germain","year":"2021","journal-title":"Biomolecules"},{"key":"10.1016\/j.cell.2024.08.034_bib67","doi-asserted-by":"crossref","DOI":"10.1038\/s41467-021-25215-0","article-title":"A transcription-based mechanism for oncogenic \u03b2-catenin-induced lethality in BRCA1\/2-deficient cells","volume":"12","author":"Dagg","year":"2021","journal-title":"Nat. Commun."},{"key":"10.1016\/j.cell.2024.08.034_bib68","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1186\/s13059-021-02390-3","article-title":"Transcription shapes DNA replication initiation to preserve genome integrity","volume":"22","author":"Liu","year":"2021","journal-title":"Genome Biol."},{"key":"10.1016\/j.cell.2024.08.034_bib69","doi-asserted-by":"crossref","DOI":"10.1038\/s41467-020-17858-2","article-title":"Topoisomerase 1 prevents replication stress at R-loop-enriched transcription termination sites","volume":"11","author":"Promonet","year":"2020","journal-title":"Nat. Commun."},{"key":"10.1016\/j.cell.2024.08.034_bib70","doi-asserted-by":"crossref","first-page":"997","DOI":"10.1038\/s41422-020-0358-x","article-title":"High-resolution mapping of mitotic DNA synthesis regions and common fragile sites in the human genome through direct sequencing","volume":"30","author":"Macheret","year":"2020","journal-title":"Cell Res."},{"key":"10.1016\/j.cell.2024.08.034_bib71","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1038\/s41586-021-03822-7","article-title":"The mutational landscape of human somatic and germline cells","volume":"597","author":"Moore","year":"2021","journal-title":"Nature"},{"key":"10.1016\/j.cell.2024.08.034_bib72","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1038\/ng.363","article-title":"Human mutation rate associated with DNA replication timing","volume":"41","author":"Stamatoyannopoulos","year":"2009","journal-title":"Nat. Genet."},{"key":"10.1016\/j.cell.2024.08.034_bib73","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/0921-8734(95)00007-S","article-title":"The somatic mutation theory of ageing","volume":"338","author":"Morley","year":"1995","journal-title":"Mutat. Res."},{"key":"10.1016\/j.cell.2024.08.034_bib74","doi-asserted-by":"crossref","first-page":"513","DOI":"10.1016\/j.cell.2005.02.003","article-title":"Senescent cells, tumor suppression, and organismal aging: good citizens, bad neighbors","volume":"120","author":"Campisi","year":"2005","journal-title":"Cell"},{"key":"10.1016\/j.cell.2024.08.034_bib75","doi-asserted-by":"crossref","first-page":"1257","DOI":"10.1126\/science.1122446","article-title":"Cellular senescence in aging primates","volume":"311","author":"Herbig","year":"2006","journal-title":"Science"},{"key":"10.1016\/j.cell.2024.08.034_bib76","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1038\/nature05949","article-title":"Delayed ageing through damage protection by the Arf\/p53 pathway","volume":"448","author":"Matheu","year":"2007","journal-title":"Nature"},{"key":"10.1016\/j.cell.2024.08.034_bib77","doi-asserted-by":"crossref","first-page":"692","DOI":"10.1038\/nrm2238","article-title":"The role of nuclear architecture in genomic instability and ageing","volume":"8","author":"Oberdoerffer","year":"2007","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"10.1016\/j.cell.2024.08.034_bib78","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1038\/nature13619","article-title":"Replication stress is a potent driver of functional decline in ageing haematopoietic stem cells","volume":"512","author":"Flach","year":"2014","journal-title":"Nature"},{"key":"10.1016\/j.cell.2024.08.034_bib79","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1002\/mas.21570","article-title":"DNA adducts: Formation, biological effects, and new biospecimens for mass spectrometric measurements in humans","volume":"39","author":"Hwa Yun","year":"2020","journal-title":"Mass Spectrom. Rev."},{"key":"10.1016\/j.cell.2024.08.034_bib80","first-page":"1507","article-title":"Deoxyguanosine adducts of t-4-hydroxy-2-nonenal are endogenous DNA lesions in rodents and humans: detection and potential sources","volume":"60","author":"Chung","year":"2000","journal-title":"Cancer Res."},{"key":"10.1016\/j.cell.2024.08.034_bib81","doi-asserted-by":"crossref","first-page":"103","DOI":"10.3934\/genet.2017.2.103","article-title":"DNA damage by lipid peroxidation products: implications in cancer, inflammation and autoimmunity","volume":"4","author":"Gentile","year":"2017","journal-title":"AIMS Genet."},{"key":"10.1016\/j.cell.2024.08.034_bib82","doi-asserted-by":"crossref","first-page":"7915","DOI":"10.1073\/pnas.90.17.7915","article-title":"Oxidants, antioxidants, and the degenerative diseases of aging","volume":"90","author":"Ames","year":"1993","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1016\/j.cell.2024.08.034_bib83","doi-asserted-by":"crossref","first-page":"10469","DOI":"10.1073\/pnas.171202698","article-title":"Does oxidative damage to DNA increase with age?","volume":"98","author":"Hamilton","year":"2001","journal-title":"Proc. Natl. Acad. Sci. US."},{"key":"10.1016\/j.cell.2024.08.034_bib84","doi-asserted-by":"crossref","first-page":"22475","DOI":"10.1073\/pnas.1012860108","article-title":"Rapid DNA-protein cross-linking and strand scission by an abasic site in a nucleosome core particle","volume":"107","author":"Sczepanski","year":"2010","journal-title":"Proc. Natl.\u00a0Acad. Sci. USA"},{"key":"10.1016\/j.cell.2024.08.034_bib85","doi-asserted-by":"crossref","first-page":"7566","DOI":"10.1093\/nar\/gkm1065","article-title":"Contributions of DNA interstrand cross-links to aging of cells and organisms","volume":"35","author":"Grillari","year":"2007","journal-title":"Nucleic Acids Res."},{"key":"10.1016\/j.cell.2024.08.034_bib86","doi-asserted-by":"crossref","first-page":"1038","DOI":"10.1038\/nature05456","article-title":"A new progeroid syndrome reveals that genotoxic stress suppresses the somatotroph axis","volume":"444","author":"Niedernhofer","year":"2006","journal-title":"Nature"},{"key":"10.1016\/j.cell.2024.08.034_bib87","doi-asserted-by":"crossref","first-page":"645","DOI":"10.1101\/gad.276261.115","article-title":"Fan1 deficiency results in DNA interstrand cross-link repair defects, enhanced tissue karyomegaly, and organ dysfunction","volume":"30","author":"Thongthip","year":"2016","journal-title":"Genes Dev."},{"key":"10.1016\/j.cell.2024.08.034_bib88","doi-asserted-by":"crossref","first-page":"23","DOI":"10.3109\/10409230903501819","article-title":"DNA interstrand crosslink repair in mammalian cells: step by step","volume":"45","author":"Muniandy","year":"2010","journal-title":"Crit. Rev. Biochem. Mol. Biol."},{"key":"10.1016\/j.cell.2024.08.034_bib89","doi-asserted-by":"crossref","first-page":"969","DOI":"10.1016\/j.cell.2008.08.030","article-title":"Mechanism of replication-coupled DNA interstrand crosslink repair","volume":"134","author":"R\u00e4schle","year":"2008","journal-title":"Cell"},{"key":"10.1016\/j.cell.2024.08.034_bib90","doi-asserted-by":"crossref","first-page":"8953","DOI":"10.1093\/nar\/gks670","article-title":"Repair of cisplatin-induced DNA interstrand crosslinks by a replication-independent pathway involving transcription-coupled repair and translesion synthesis","volume":"40","author":"Enoiu","year":"2012","journal-title":"Nucleic Acids Res."},{"key":"10.1016\/j.cell.2024.08.034_bib91","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1186\/1755-8794-5-38","article-title":"Structural, functional and molecular analysis of the effects of aging in the small intestine and colon of C57BL\/6J mice","volume":"5","author":"Steegenga","year":"2012","journal-title":"BMC Med. Genomics"},{"key":"10.1016\/j.cell.2024.08.034_bib92","doi-asserted-by":"crossref","DOI":"10.1038\/s41598-019-46966-3","article-title":"Transcriptome analysis identifies a robust gene expression program in the mouse intestinal epithelium on aging","volume":"9","author":"Kazakevych","year":"2019","journal-title":"Sci. Rep."},{"key":"10.1016\/j.cell.2024.08.034_bib93","doi-asserted-by":"crossref","first-page":"590","DOI":"10.1038\/s41586-020-2496-1","article-title":"A single-cell transcriptomic atlas characterizes ageing tissues in the mouse","volume":"583","year":"2020","journal-title":"Nature"},{"key":"10.1016\/j.cell.2024.08.034_bib94","doi-asserted-by":"crossref","DOI":"10.1111\/acel.13562","article-title":"Different responses to DNA damage determine ageing differences between organs","volume":"21","author":"Vougioukalaki","year":"2022","journal-title":"Aging Cell"},{"key":"10.1016\/j.cell.2024.08.034_bib95","doi-asserted-by":"crossref","first-page":"466","DOI":"10.1038\/nature23470","article-title":"Mitotic progression following DNA damage enables pattern recognition within micronuclei","volume":"548","author":"Harding","year":"2017","journal-title":"Nature"},{"key":"10.1016\/j.cell.2024.08.034_bib96","doi-asserted-by":"crossref","first-page":"3926","DOI":"10.1172\/JCI96519","article-title":"ATR kinase inhibitor AZD6738 potentiates CD8+ T\u00a0cell-dependent antitumor activity following radiation","volume":"128","author":"Vendetti","year":"2018","journal-title":"J.\u00a0Clin. Invest."},{"key":"10.1016\/j.cell.2024.08.034_bib97","doi-asserted-by":"crossref","first-page":"2933","DOI":"10.1158\/0008-5472.CAN-18-2807","article-title":"Inhibition of ataxia-telangiectasia mutated and RAD3-related (ATR) overcomes oxaliplatin resistance and promotes antitumor immunity in colorectal cancer","volume":"79","author":"Comb\u00e8s","year":"2019","journal-title":"Cancer Res."},{"key":"10.1016\/j.cell.2024.08.034_bib98","doi-asserted-by":"crossref","first-page":"3392","DOI":"10.1158\/1078-0432.CCR-18-1821","article-title":"ATR inhibition potentiates the radiation-induced inflammatory tumor microenvironment","volume":"25","author":"Dillon","year":"2019","journal-title":"Clin. Cancer Res."},{"key":"10.1016\/j.cell.2024.08.034_bib99","doi-asserted-by":"crossref","DOI":"10.15252\/embj.2019104036","article-title":"ATR inhibition potentiates ionizing radiation-induced interferon response via cytosolic nucleic acid-sensing pathways","volume":"39","author":"Feng","year":"2020","journal-title":"EMBO J."},{"key":"10.1016\/j.cell.2024.08.034_bib100","doi-asserted-by":"crossref","first-page":"4864","DOI":"10.1002\/cam4.5109","article-title":"Immunogenicity of small-cell lung cancer associates with STING pathway activation and is enhanced by ATR and TOP1 inhibition","volume":"12","author":"Li","year":"2023","journal-title":"Cancer Med."},{"key":"10.1016\/j.cell.2024.08.034_bib101","doi-asserted-by":"crossref","DOI":"10.1038\/s41467-017-00221-3","article-title":"ATR inhibition facilitates targeting of leukemia dependence on convergent nucleotide biosynthetic pathways","volume":"8","author":"Le","year":"2017","journal-title":"Nat. Commun."},{"key":"10.1016\/j.cell.2024.08.034_bib102","doi-asserted-by":"crossref","DOI":"10.1016\/j.celrep.2022.111371","article-title":"Thymidine rescues ATR kinase inhibitor-induced deoxyuridine contamination in genomic DNA, cell death, and interferon-\u03b1\/\u03b2 expression","volume":"40","author":"Sugitani","year":"2022","journal-title":"Cell Rep."},{"key":"10.1016\/j.cell.2024.08.034_bib103","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1002\/cyto.a.24714","article-title":"OMIP-088: Twenty-target imaging mass cytometry panel for major cell populations in mouse formalin fixed paraffin embedded liver","volume":"103","author":"Birrer","year":"2023","journal-title":"Cytometry A"},{"key":"10.1016\/j.cell.2024.08.034_bib104","series-title":"napari: a multi-dimensional image viewer for Python","author":"Ahlers","year":"2023"},{"key":"10.1016\/j.cell.2024.08.034_bib105","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1038\/s41592-020-01018-x","article-title":"Cellpose: a generalist algorithm for cellular segmentation","volume":"18","author":"Stringer","year":"2021","journal-title":"Nat. Methods"},{"key":"10.1016\/j.cell.2024.08.034_bib106","doi-asserted-by":"crossref","first-page":"3565","DOI":"10.1038\/s41596-023-00881-0","article-title":"An end-to-end workflow for multiplexed image processing and analysis","volume":"18","author":"Windhager","year":"2023","journal-title":"Nat. Protoc."}],"container-title":["Cell"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0092867424009632?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0092867424009632?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2024,11,14]],"date-time":"2024-11-14T00:20:55Z","timestamp":1731543655000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0092867424009632"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,10]]},"references-count":106,"journal-issue":{"issue":"22","published-print":{"date-parts":[[2024,10]]}},"alternative-id":["S0092867424009632"],"URL":"https:\/\/doi.org\/10.1016\/j.cell.2024.08.034","relation":{},"ISSN":["0092-8674"],"issn-type":[{"value":"0092-8674","type":"print"}],"subject":[],"published":{"date-parts":[[2024,10]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"In\u00a0vivo DNA replication dynamics unveil aging-dependent replication stress","name":"articletitle","label":"Article Title"},{"value":"Cell","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.cell.2024.08.034","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2024 The Author(s). Published by Elsevier Inc.","name":"copyright","label":"Copyright"}]}}